The topic of the present study is the establishment of a plasmid-mediated mutation assay system which allows us to determine changes in DNA sequence. These changes are directly correlated with the mutagenized function a specific gene. Pretreatment of plasmid DNA with carcinogen prior to transfection into E. coli permits us to assay mutation with no toxic effect from drugs. Alternatively, the plasmid can be transfected into E. coli followed by exposure to carcinogen with or without the microsome fraction of rat liver depending on the drugs' requirements for metabolic activation. Mutated plasmid DNAs isolated and cloned individually are investigated for determination of the chemical nature of DNA modification. The altered genetic functions of mutagenized plasmid DNA are tested by repeated transfection of the DNA into E. coli.